2K01

Structure of a locked SDF1 dimer

2K01 の概要

• エントリーDOI: 10.2210/pdb2k01/pdb
• NMR情報: BMRB: 15633
• 分子名称: Stromal cell-derived factor 1 (1 entity in total)
• 機能のキーワード: stromal cell derived factor-1, sdf1-alpha, cxcl12, chemokine, sulfotyrosine, locked dimer, alternative splicing, chemotaxis, cytokine, growth factor, secreted
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16377.52

構造登録者

Volkman, B.F.,Veldkamp, C.T.,Peterson, F.C. (登録日: 2008-01-23, 公開日: 2008-10-28, 最終更新日: 2023-06-14)

主引用文献

Veldkamp, C.T.,Seibert, C.,Peterson, F.C.,De la Cruz, N.B.,Haugner, J.C.,Basnet, H.,Sakmar, T.P.,Volkman, B.F.
Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12
Sci.Signal., 1:ra4-ra4, 2008

PubMed Abstract: Stem cell homing and breast cancer metastasis are orchestrated by the chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4. Here, we report the nuclear magnetic resonance structure of a constitutively dimeric SDF-1 in complex with a CXCR4 fragment that contains three sulfotyrosine residues important for a high-affinity ligand-receptor interaction. CXCR4 bridged the SDF-1 dimer interface so that sulfotyrosines sTyr7 and sTyr12 of CXCR4 occupied positively charged clefts on opposing chemokine subunits. Dimeric SDF-1 induced intracellular Ca2+ mobilization but had no chemotactic activity; instead, it prevented native SDF-1-induced chemotaxis, suggesting that it acted as a potent partial agonist. Our work elucidates the structural basis for sulfotyrosine recognition in the chemokine-receptor interaction and suggests a strategy for CXCR4-targeted drug development.

PubMed: 18799424
DOI: 10.1126/scisignal.1160755

実験手法

SOLUTION NMR